Busulfan in Treating Children and Adolescents With Refractory CNS Cancer

Lymphoma Clinical Trial

Official title:

Phase I Study of Intrathecal Spartaject-Busulfan in Children With Neoplastic Meningitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006246
• Other study ID #: CDR0000068178
• Secondary ID: PBTC-004
• Status: Completed
• Phase: Phase 1
• First received: September 11, 2000
• Last updated: October 6, 2009
• Start date: November 2000

Study information

• Verified date: October 2009
• Source: Pediatric Brain Tumor Consortium
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the safety of delivering intrathecal busulfan in children and adolescents who have refractory CNS cancer and to estimate the maximum tolerated dose of this treatment regimen.

Description:

OBJECTIVES:

• Determine the qualitative and quantitative toxicities of intrathecally administered busulfan in children and adolescents with refractory CNS malignancies.

• Determine the maximum tolerated dose of this treatment regimen in these patients.

• Determine the cerebrospinal fluid and serum pharmacokinetics of this treatment regimen in these patients.

• Determine the efficacy of this treatment regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive intrathecal busulfan twice a week, at least 3 days apart, for 2 weeks. Patients with complete or partial response or stable disease may continue therapy once a week for 2 weeks, once a week every other week for 2 treatments, and then once a month thereafter in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of busulfan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities.

Patients are followed every 3 months for the first year, every 6 months for 4 years, and then annually for 5 years.

PROJECTED ACCRUAL: Approximately 18-24 patients will be accrued for this study over 18-38 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. primary completion date: May 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 21 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed CNS malignancy, including any of the following:

• Primary malignant brain tumor refractory to standard therapy and metastatic to the cerebrospinal fluid (CSF) or leptomeningeal subarachnoid space

• Recurrent or persistent leptomeningeal leukemia, lymphoma, or germ cell tumor refractory to conventional therapy

• In second or greater relapse

• CSF white blood count greater than 5 cells/mm3 with blasts on cytospin OR

• Evidence of leptomeningeal tumor by MRI

• No concurrent bone marrow disease

• No obstruction or compartmentalization of CSF flow on CSF flow study

PATIENT CHARACTERISTICS:

Age:

• 3 to 21

Performance status:

• Lansky 50-100% (under 10 years)

• Karnofsky 50-100% (10 to 21 years)

Life expectancy:

• Greater than 8 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3

• Platelet count greater than 75,000/mm^3

Hepatic:

• Bilirubin normal for age

• ALT and AST less than 5 times upper limit of normal (ULN)

• No hepatic disease

Renal:

• Creatinine no greater than 1.5 times ULN OR

• Glomerular filtration rate greater than 70 mL/min

• No renal disease

Cardiovascular:

• No cardiac disease

Pulmonary:

• No pulmonary disease

Other:

• No uncontrolled infection

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)

• At least 1 week since prior intrathecal chemotherapy (2 weeks for cytarabine) and recovered

• Evidence of subsequent disease progression

• Concurrent systemic chemotherapy allowed for recurrent disease after first course of treatment except for the following:

• Chemotherapy targeted at leptomeningeal disease

• Other phase I agent

• Any agent that significantly penetrates the CSF (e.g., high dose methotrexate greater than 1 g/m2, thiotepa, high dose cytarabine, fluorouracil, IV mercaptopurine, nitrosoureas, or topotecan)

• Any agent that causes serious unpredictable CNS side effects

Endocrine therapy:

• Prior dexamethasone allowed with decreasing or stable dose at least one week before study

• Concurrent dexamethasone or prednisone with chemotherapy regimen allowed

Radiotherapy:

• At least 1 week since prior focal irradiation to the brain or spine

• At least 8 weeks since prior craniospinal irradiation

• No concurrent cranial or craniospinal irradiation

Surgery:

• Not specified

Other:

• No other concurrent intrathecal or systemic therapy for leptomeningeal disease

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Childhood Germ Cell Tumor
• Leukemia
• Lymphoma
• Metastatic Cancer
• Neoplasm Metastasis
• Nervous System Neoplasms
• Retinoblastoma
• Sarcoma

Intervention

Drug:
• busulfan

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Pediatric Brain Tumor Consortium	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Gururangan S, Petros WP, Poussaint TY, Hancock ML, Phillips PC, Friedman HS, Bomgaars L, Blaney SM, Kun LE, Boyett JM. Phase I trial of intrathecal spartaject busulfan in children with neoplastic meningitis: a Pediatric Brain Tumor Consortium Study (PBTC- — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicities of IT administered busulfan in children and adolescents with refractory CNS malignancies			Yes
Primary	Maximum tolerated dose of IT administered busulfan			Yes
Primary	Serum and CSF pharmacokinetics of IT administered busulfan			No